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Diss Factsheets

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report date:
2012

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Reference substance name:
54074-94-1
Cas Number:
54074-94-1
IUPAC Name:
54074-94-1
Constituent 2
Reference substance name:
isopropyl-3-hydroxybutyrate
IUPAC Name:
isopropyl-3-hydroxybutyrate
Test material form:
other: colorless liquid
Details on test material:
The test substance, identified as Isopropyl-3-hydroxybutyrate, Code#: 54074-94-1, was received on May 4, 2012 and was further identified with PSL Reference Number 120504-3D. The test substance was stored at room temperature. The sample was applied as received. Documentation of the methods of synthesis, fabrication, or derivation of the test substance is retained by the Sponsor. The following information related to the characterization of the test substance was provided by the Sponsor:
Composition: Isopropyl-3-hydroxybutyrate > 99.9% (CAS #54074-94-1)
Physical Description: Colorless liquid
Solubility: Soluble in water.
Stability: Test substance was expected to be stable for the duration of testing.
Expiration Date: Not applicable.

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
4.A.1 Housing: The animals were singly housed in suspended stainless steel caging with mesh floors, which conform to the size recommendations in the most recent Guide for the Care and Use of Laboratory Animals (Natl. Res. Council, 2011 ). Litter paper was placed beneath the cage and was changed at least three times per week.

Animal Room Temperature and Relative Humidity Ranges: 19-22°C and 48-70%, respectively.

Animal Room Air Changes/Hour: 14 Airflow measurements are evaluated regularly and the records are kept on file at Product Safety Labs.

Photoperiod: 12-hour light/dark cycle

Acclimation Period: 7 days

Food: Harlan Teklad Global 16% Protein Rodent Diet® #2016. The diet was available ad libitum.

Water: Filtered tap water was supplied ad libitum by an automatic water dispensing system.

Contaminants: There were no known contaminants reasonably expected to be found in the food or water at levels which would have interfered with the results of this study. Analyses of the food and water are conducted regularly and the records are kept on file at Product Safety Labs.

IDENTIFICATION
Cage: Each cage was identified with a cage card indicating at least the study number and identification and sex of the animal.

Animal: A number was allocated to each rat on receipt and a stainless steel ear tag bearing this number was attached to the animal. This number, together with a sequential animal number assigned to study 34438, constituted unique identification.

Administration / exposure

Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
Preparation and Selection of Animals
On the day prior to application, a group of animals was prepared by clipping the dorsal area and the trunk. After clipping and prior to application, the animals were examined for health, weighed (initial) and the skin checked for any abnormalities. Ten healthy naive rats (five males and five females; not previously tested) were selected for test.

Dose Calculations
Individual doses were calculated based on the initial body weights, taking into account the density (determined by PSL) of the test substance.

Application of Test Substance
Five thousand mg/kg of body weight of the test substance was applied evenly over a dose area of approximately 2 inches x 3 inches (approximately 10% of the body surface) and covered with a 2-inch x 3-inch, 4-ply gauze pad. The gauze pad and entire trunk of each animal were then wrapped with 3-inch Durapore tape to avoid dislocation of the pad and to minimize loss of the test substance. The rats were then returned to their designated cages. The day of application was considered Day 0 of the study. After 24 hours of exposure to the test substance, the pads were removedand the test sites were gently cleansed of any residual test substance.

Duration of exposure:
24 hours
Details on study design:
Body Weights
Individual body weights of the animals were recorded prior to test substance application (initial) and again on Days 7 and 14 (termination).

Cage-Side Observations
The animals were observed for mortality, signs of gross toxicity, and behavioral changes during the first several hours after application and at least once daily thereafter for 14 days. Observations included gross evaluation of skin and fur, eyes and mucous membranes, respiratory, circulatory, autonomic and central nervous systems, somatomotor activity and behavior pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhea, and coma.

Necropsy
All rats were euthanized via C02 inhalation on Day 14. Gross necropsies were performed on all animals. Tissues and organs of the thoracic and abdominal cavities were examined.

Results and discussion

Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Sex:
male/female
Dose descriptor:
LD0
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
none
Clinical signs:
other: All animals survived exposure to the test substance and gained body weight during the study. Other than the dermal irritation noted at six dose sites between Days 1 and 2, there were no other clinical findings recorded for any animal over the course of th
Gross pathology:
no abnormalities observed

Applicant's summary and conclusion

Interpretation of results:
practically nontoxic
Remarks:
Migrated information
Conclusions:
Under the conditions of this study, the single dose acute dermal LD50 of Isopropyl-3-hydroxybutyrate is greater than 5,000 mg/kg of body weight in male and female rats.
Executive summary:

An acute dermal toxicity test was conducted with rats to determine the potential for Isopropyl-3- hydroxybutyrate to produce toxicity from a single topical application. Under the conditions of this study, the single dose acute dermal LD50 of the test substance is greater than 5,000 mg/kg of body weight in male and female rats. Five thousand milligrams of the test substance per kilogram of body weight was applied to the skin of ten healthy rats for 24 hours. The animals were observed for mortality, signs of gross toxicity, and behavioral changes at least once daily for 14 days. Body weights were recorded prior to application and again on Days 7 and 14 (termination). Necropsies were performed on all animals at terminal sacrifice. All animals survived exposure to the test substance and gained body weight during the study. Other than the dermal irritation noted at six dose sites between Days 1 and 2, there were no other clinical findings recorded for any animal over the course of the study. No gross abnormalities were noted for any of the animals when necropsied at the conclusion of the 14-day observation period.